Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart

In contrast to healthy volunteers, regional differences of cardiac autonomic innervation have been described through the use of C11-hydroxyephedrine positron emission tomography (HED-PET) in the left ventricles of patients with dilated cardiomyopathy. The goal of the present study was to correlate HED-PET images with biochemical analysis of tissue samples. To assess the significance of altered HED uptake, we used HED-PET to examine eight patients with dilated cardiomyopathy before heart transplantation. After explantation, we measured the density and affinity of uptake1 (3H-mazindol binding) and tissue norepinephrine content as markers of presynaptic function, and we determined beta-receptor density and affinity (3H-CGP 12177 binding) in the corresponding areas of the same patients. The density of uptake1 and norepinephrine content showed marked regional variation, with highest values in the anterior septal wall and lowest in inferoapical and apical areas. Both parameters were closely correlated (r=.65, P=.05). Similarly, uptake1 density or norepinephrine content and HED retention (PET) showed clear correlations (r=.63 and .60, respectively). Uptake1 affinities did not vary significantly and were not correlated to the other parameters. Beta-Adrenergic receptor density showed some, albeit less pronounced, regional variation and was weakly correlated to uptake1 density and local HED retention (r=.38 and .31, respectively). Uptake1 density and tissue norepinephrine content showed marked regional variation in cardiomyopathic left ventricles. HED-PET is significantly correlated to the density but not the affinity of uptake1 sites in the human heart, suggesting either loss of neurons or downregulation of uptake1 in dilated cardiomyopathy. HED-PET is a valuable marker for alterations of the presynaptic sympathoadrenergic system in humans.